The candidate received residency training in Pediatrics and Anesthesiology, and subspeciality training in Pediatric Critical Care Medicine, during which he was instrumental in developing an infant pediatric cardiopulmonary resuscitation (CPR) model in piglets. Presently, in addition to patient care and teaching activities, on the Anestesia and Critical Care faculty the candidate has been a major participant in the laboratories of Dr. Richard Traystman (sponsor of the candidate) performing CPR experiments. During prolonged CPR in infants, neither cerebral blood flow (CBF) nor cerebral metabolism is sustained. Prolonged CPR in infants is an important clinical issue because of the long periods that infants often need CPR administered and the poor outcome frequently obtained following cardiac arrest and CPR. In aim 1, the mechanism of this failure will be evaluated and mechanical maneuvers designed to preserve CBF and cerebral O2 uptake will be tested. In aim 2 we will determine if equipotent doses of different classes of adrenergic drugs given during CPR have different effects on the recovery of cerebral metabolism, regional CBF and electrical function. We will find out if the blood brain barrier is disrupted during CPR or during the cerebral hyperemia that follows cardioversion, or if circulating epinephrine gains entry into the brain by saturating the enzymatic barrier for catecholamines. After a period of cardiac arrest, external chest compression partially reestablishes CBF until the circulation is fully restored by cardioversion. Depending on the level of CBF attained during CPR, partial cerebral ischemia may continue. Reperfusion injury associated with O2 derived free radical production may begin with CPR. In aim 3, we will determine whether modest levels of cerebral reoxygenation achieved with CPR generates superoxide radical and if cerebral O2 delivery must reach a critical level for free radical generation to occur, comparing this to full reperfusion following cardioversion. In aim 4, we will determine how free radical scavengers can best be administered during CPR to inhibit free radical appearance and whether these agents during CPR improves recovery and brain metabolism, electrical function, CBF and neurological outcome. These studies will add much to the clinical practice of CPR in infants. In addition, the CIA will provide experience and supervision which will facilitate the applicant's development as an effective and independent investigator.